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Respiratory fungal infection

Color index: ● Important ● Doctor Notes ● Extra, TN

Respiratory Block - Microbiology Team 438 Objectives :

● Acquire the basic knowledge about fungal infections of the respiratory system

● Know the main fungi that affects the respiratory system.

● Identify the clinical settings of such infections.

● Know the laboratory diagnosis, and treatment of these infections. Introduction

● inhalation (airborne), and Aspiration (oral route), are mostly the rout of Respiratory infections. ● Respiratory fungal infections are less common than viral and bacterial infections. Viruses > bacteria > fungi. ● Invasive diseases have significant difficulties in diagnosis and treatment.

Opportunistic : Diseases in immunocompromised host. Ex, HIV/AIDS Primary infections : caused by primary pathogen. Etiology Opportunistic Primary infections

Yeast “Filamentous”Mould fungi Dimorphic fungi ( pathogen → disease ) ( pathogen → disease ) “both and mould fungi”

● Candida → very rare ● species → ● ● ● Zygomycetes, and → ● Blastomyces dermatitidis

and C. gattii → Usually Zygomycosis ● Paracoccidioides brasiliensis seen in meningitis rather than resp ● Other mould ● immitis C : Cryptococcus Primary Systemic Mycoses

Primary Systemic Mycoses

Definition Infections of the respiratory system.

Transmission Inhalation

Where can we see it ? Dissemination “it can spread to more than organ” seen in immunocompromised hosts. “Severe”

Where can we find it ? Common in North America to a lesser extent in South America. Not common in other parts of the World.

In nature found in soil of restricted habitats. Primary pathogens. They are highly infectious. “If you inhaled just few of it you will get infected unlike others” Etiology it include: = ● Dimorphic fungi ● ● ● Aspergillosis Definition it include Aspergillosis is a spectrum of diseases of Mycotoxicosis, Colonization (without invasion and extension) in humans and animals caused by members of the preformed cavities. Invasive disease of lungs., Systemic and genus Aspergillus (mould fungi). disseminated disease, Allergy.

Etiology Risk factor Diagnosis Treatment

Aspergillus species, ● Bone marrow/ organ Specimen: : 1 2 common species are : ● Respiratory specimens: Sputum, BAL, Voriconazole transplantation 3 ● A.fumigatu Lung biopsy. “the drug of choice” most virulent Because we gave them immunosuppressants ● Other samples: Blood Alternative therapy: to decrease their immunity ● A. flavus Lab. Investigations: (image slide 8) , most common in Riyadh ● Cancer: Leukemia, Itraconazole, ● ● Direct Microscopy: Giemsa Stain, 4GMS A. niger lymphoma. Caspofungin ● A. terreusand Stain. Will show fungal septate hyphae ● AIDS + to remove ● A. nidulans. ● Culture on SDA. ● Drugs: Cytotoxic Aspergillus is first (image slide 8) Serology: common fungal pathogen drugs, steroids. in respiratory infection. ● Test for Antibody. ● Diabetes ● ELISA test for galactomannan ● Others 1- NOT the best because it’s full with Antigen.”specific for Aspergillus” normal flora 2- BronchoAlveolar Lavage Second PCR: Detection of Aspergillus DNA in clinical best method 3- The BEST method because it’s samples. sterile + you can check if the disease is invasive or not 4- Grocott Methenamine Silver Classification of Aspergillosis Pathogenesis: Airways/Nasal exposure to airborne Aspergillus.

Types Causes Signs and symptom Diagnosis

● Cough Invasive pulmonary ● hemoptysis Radiology: will show lesions with halo sign. Aspergillosis ● fever In immunocompromised patient ● Leukocytosis (Image slide 8)

● Aspergilloma of lung Aspergilloma​ ,​ ● Dry Cough which is also ● hemoptysis Radiology: will show mass in the lung. Chronic Aspergillosis ● Maxillary (sinus) known as ● variable fever radiolucent crescent”air surround the mass” “Colonizing Aspergillosis” aspergilloma (Aspergillus ball). (Image slide 8)

● Allergic ● Symptoms of Asthma ● test reactivity to Aspergillus bronchopulmonary ● Bronchial obstruction ● Serum antibodies to Aspergillus Allergic Aspergillosis (ABPA) ● -In healthy patient usually Eosinophilia This test is used to differentiate between asthma and allergic aspergillosis -common in KSA ● Allergic Aspergillus ● Wheezing +/- ● Serum IgE> 1000 ng/ml sinusitis

Persistence without colonisation of the airways or disease nose/ sinuses. Fungal sinusitis Common in KSA especially allergic synasitis

Aspergillus sinusitis has the same spectrum of aspergillus disease in the lung.

Symptoms Etiology Complication Diagnosis Treatment

Nasal polyps and Aspergillus flavus In immunocompromised, ● Clinical and Radiology Depends on : other symptoms and other fungi. Could disseminate to eye ● Histology ● the type and severity of of sinusitis. lead to craneum ● Culture the disease. (Rhinocerebral)”Brain ”. ● the immunological status ● Precipitating antibodies of the patient. useful in diagnosis ● Measurement of IgE Aspergillus flavus is the most common cause in KSA level, RAST test Diagnosis of Aspergillosis Visuals Chronic and Invasive

Chronic Aspergillosis, Note the Air crescent Invasive pulmonary aspergillosis, Note the Halo sign

Common airborne Fungi Lab. Investigations of Aspergillosis (differ by color after culturing) Types of Aspergillus

Smear: Septate fungal Cultures of Aspergillus hyphae Aspergillosis (black-brownish) Aspergillus niger Aspergillus fumigatus (greenish-yellow) Zygomycosis

Pulmonary zygomycosis Rhinocerebral zygomycosis

● Acute infection ● Marked by : Consolidation , nodules , cavitation , pleural effusion , hemoptysis ● Infection may extend to chest wall , diaphragm , pericardium causing : - Pulmonary infarction and hemorrhage - Rapid evolving clinical course

Early recognition and intervention are critical If it’s in the form of sinusitis it will extends into the brain in 10 days Pulmonary Zygomycosis

Etiology Risk factors Diagnosis Treatment

● Amphotericin B ● Transplant Specimen: ● Surgery patients ● Respiratory specimens: Sputum, BAL, Lung

● Malignancy biopsy + other samples Zygomycetes : Laboratory Investigations: Non-septate ● AIDS ● ➢ hyphae ● Diabetic Direct Microscopy: Giemsa stain, GMS stain Will show broad non- septate fungal hyphae e.g. Rhizopus ketoacidosis ● Culture on SDA (no cycloheximide)

Serology: Not available And many others

GMS stain for zygomycetes (PCP)

Pneumocystis pneumonia (PCP) is Opportunistic fungal pneumonia

It is interstitial pneumonia of the alveolar area. Affect compromised host ( Especially common in AIDS patients ) . Etiology Diagnosis Treatment

● Does not grow in laboratory media e.g. SDA ● Trimethoprim”the drug of Pneumocystis jiroveci ● Laboratory Diagnosis: choice” – sulfamethoxazole

- specimen : Bronchoscopic specimens (BAL) ● Dapsone

BronchoAlveolar Lavage, Sputum, Lung , biopsy tissue. -Naturally found in rodents

(rats), other animals(goats, ● Histological sections or smears stained by horses), Humans may - GMS stain. contract it during childhood - Immunofluorescence (better sensitivity)

If positive —> will see cysts of hat-shape, cup shape, crescent

Cysts Summary

Primary Systemic Zygomycosis Pneumocystosis Aspergillosis (PCP) is Pulmonary zygomycosis Mycoses Opportunistic fungal pneumonia.

Cough - hemoptysis - fever Epidemiology/ Highly infectious , Invasive : leukocytosis Acute infection marked by Consolidation, It is interstitial pneumonia of the signs and common in America Allergic : asthma symptoms nodules, cavitation, pleural effusion, alveolar area. symptoms but not here Chronic : aspergilloma hemoptysis.Risk factor: Diabetes. Risk factor: AIDS patients. Fungal sinusitis : nasal polyps

Etiology Dimorphic fungi A.fumigatus, A.flavus Zygomycetes Pneumocystis jiroveci

1-Specimen: Sputum, BAL, Lung biopsy. 2-Lab. Investigations: 1- Specimen : BAL (GMS)→ septate fungal hyphae 2-Laboratory Investigations: 3-Serology: ELISA test for 1-Specimen: Sputum, BAL, Lung biopsy Histological sections or smears stained galactomannan Antigen. 2-Laboratory Investigations: Diagnosis by (GMS) stain and Immunofluorescence Allergic and sinusitis : IgE serum (GMS)→ broad non-septate fungal hyphae (better sensitivity) 4-PCR detect the DNA of aspergillus. 3-Serology: Not available If positive —> cysts 5- Radiology Does not grow in laboratory media. Invasive: halo sign Chronic : mass with crescent

Treatment Antifungal: Voriconazole Amphotericin B, Surgery Trimethoprim 1.A 2.C 3.A 4.B 5.C Quiz :

1) Which one is considered highly infectious ? Q1. A 55-year-old man who recently recovered uneventfully from a heart valve transplant presents to the emergency room A.Coccidioidomycosis B. Aspergillus niger C. Rhizopus with pleuritic chest pain, hemoptysis, fever, and chills. While he is being examined, he has a myocardial infarction and the 2) All have abnormal level of IgE except medical team is unable to revive him. An autopsy revealed

A.Aspergillus sinusitis B. allergic aspergillosis C. Pulmonary Zygomycosis septate hyphae in many tissues, what is the likely diagnosis ?

3) One of the following considered as an acute infection Aspergillosis

A.pulmonary zygomycosis B. Pneumocystosis C. Fungal sinusitis Q2. A 57-year-old diabetic patient came to the hospital with a fever , headache and coughing blood , the laboratory diagnoses 4) Which one of the following can’t be cultured showed non-septate hyphae , what is the best treatment for in this condition ? A.Aspergillus flavus B. Pneumocystis jiroveci C. Rhizopus

5) A patient’s lab diagnosis show septate hyphae , which is : Amphotericin B A.Zygomycetes B. Pneumocystis jiroveci C. Aspregillus fumigatus Team Leaders

Badr AlQarni Renad AlMutawa

Team Sub-Leader T Abdullah Alassaf

This lecture is done by:

Team Members

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★ Faisal Alkoblan ★ Noura Almazrou ★ Faris Almubarak ★ Rema Almutawa ★ Alwaleed Alazmi ★ Elaf Almusahel ★ Mohammed Alshoieer ★ Lina Alosaimi ★ abdullah Alothman ★ Ghada Alsadhan Contact us: ★ Faisal Alzahrani ★ Sarah Alhelal ★ Abdullah Alzamil ★ Amirah Alzahrani ★ Rawan Alzayed ★ Sarah Alkhalife Editing [email protected] file